Overview

My group works on methods to recapitulate human, chimpanzee and other great ape development in controlled cell culture environments using three-dimensional (3D) organoids and other stem cell-based systems. We integrate multiple methods including tissue engineering, gene editing, high-throughput confocal microscopy, single-cell genomics, and comparative genomics. We want to understand how human cells are unique from our closest living and extinct relatives, how they vary in human populations around the world, and how they fail in human disease. More detail describing on-going projects can be found below:

1. Great ape organoids

Complex, multi-lineage, 3D organ-like tissues (so called “organoids”) can be generated using pluripotent stem cells from human, chimpanzee and other great apes. We are using single-cell genomics on human, chimp, and other great ape organoids to uncover features that are unique to human developmental programs.

2. Neandertalized cells

We are working with other groups in the department to revert modern human DNA in human stem cells back to the ancestral state to create “Neandertalized” stem cell lines. We will use these cells to understand the physiological impact of genetic change on the modern human lineage.

3. High-throughput cellular phenotyping

We are developing high-throughput strategies to use CRISPR-Cas9 editing in combination with single-cell transcriptomics and confocal imaging to understand how genetic change affects neuron and hepatocyte cell biology.

4. Organ malformation

We are using 3D organoids to understand how rare human genetic diseases perturb gene networks controlling human development, with particular focus on the cortex and liver.